Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells
Open Access
- 5 August 2013
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 110 (34), 13869-13874
- https://doi.org/10.1073/pnas.1222341110
Abstract
Neural precursor cells of the central nervous system undergo successive temporal waves of terminal division, each of which is soon followed by the onset of cell differentiation. The organ of Corti in the mammalian cochlea develops differently, such that precursors at the apex are the first to exit from the cell cycle but the last to begin differentiating as mechanosensory hair cells. Using a tissue-specific knockout approach in mice, we show that this unique temporal pattern of sensory cell development requires that the adjacent auditory (spiral) ganglion serve as a source of the signaling molecule Sonic hedgehog (Shh). In the absence of this signaling, the cochlear duct is shortened, sensory hair cell precursors exit from the cell cycle prematurely, and hair cell differentiation closely follows cell cycle exit in a similar apical-to-basal direction. The dynamic relationship between the restriction of Shh expression in the developing spiral ganglion and its proximity to regions of the growing cochlear duct dictates the timing of terminal mitosis of hair cell precursors and their subsequent differentiation.Keywords
This publication has 34 references indexed in Scilit:
- Dynamic expression pattern of Sonic hedgehog in developing cochlear spiral ganglion neuronsDevelopmental Dynamics, 2010
- Neurogenin 1 (Neurog1) expression in the ventral neural tube is mediated by a distinct enhancer and preferentially marks ventral interneuron lineagesDevelopmental Biology, 2010
- The Small GTPase Rac1 Regulates Auditory Hair Cell MorphogenesisJournal of Neuroscience, 2009
- Deletion of Atoh1 Disrupts Sonic Hedgehog Signaling in the Developing Cerebellum and Prevents MedulloblastomaScience, 2009
- Hedgehog Signaling Regulates Sensory Cell Formation and Auditory Function in Mice and HumansJournal of Neuroscience, 2008
- Opposing gradients of Gli repressor and activators mediate Shh signaling along the dorsoventral axis of the inner earDevelopment, 2007
- Cellular growth and rearrangement during the development of the mammalian organ of CortiDevelopmental Dynamics, 2004
- Identification of Vangl2 and Scrb1 as planar polarity genes in mammalsNature, 2003
- Vertebrate neural cell-fate determination: Lessons from the retinaNature Reviews Neuroscience, 2001
- Actin Filaments, Stereocilia, and Hair Cells: How Cells Count and MeasureAnnual Review of Cell and Developmental Biology, 1992